Maintaining level of modifiable dementia risk scores is associated with better cognitive outcomes than increasing risk scores: A population-based prospective cohort study.

Background: A brain healthy lifestyle, consisting of good cardiometabolic health and being cognitively and socially active in midlife, is associated with a lower risk of cognitive decline years later. However, it is unclear whether lifestyle changes over time also affect the risk for mild cognitive impairment (MCI)/dementia, and rate of cognitive decline.

Objectives: To investigate if lifestyle changes over time are associated with incident MCI/dementia risk and rate of cognitive decline.

Nivolumab combination therapies in patients with advanced gastric and gastroesophageal junction cancer: the phase II FRACTION gastric cancer study.

Background: Nivolumab-based therapies are efficacious with acceptable safety in patients with gastric cancer (GC) and gastroesophageal junction cancer (GEJC). Novel nivolumab-based combination immunotherapies may offer enhanced efficacy in these indications. FRACTION-GC was a signal-seeking, randomized, open-label, phase II adaptive-design trial assessing efficacy and safety of nivolumab in combination with ipilimumab [cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody], relatlimab (lymphocyte-activation gene 3 antibody), or IDO1i (BMS986205, an indoleamine-2,3-dioxygenase-1 inhibitor) in patients with unresectable, advanced/metastatic GC/GEJC.

Six months of hybrid closed-loop therapy improves diabetes-specific positive well-being, and reduces diabetes distress and fear of hypoglycemia: secondary analysis of a randomized controlled trial.

Introduction: This analysis aimed to investigate diabetes-specific psychological outcomes among adults with type 1 diabetes (T1D) using hybrid closed-loop (HCL) versus standard therapy.

Research Design And Methods: In this multicenter, open-label, randomized, controlled, parallel-group clinical trial, adults with T1D were allocated to 26 weeks of HCL (MiniMed™ 670G) or standard therapy (insulin pump or multiple daily injections without real-time continuous glucose monitoring). Psychological outcomes (awareness and fear of hypoglycemia; and diabetes-specific positive well-being, diabetes distress, diabetes treatment satisfaction, and diabetes-specific quality of life (QoL)) were measured at enrollment, mid-trial and end-trial.

Laboratory Assessment of Factor VIII Inhibitors: When Is It Required? A Perspective Informed by Local Practice.

This perspective discusses the critical role of laboratory assessments in assessing factor VIII (FVIII) inhibitors. These are auto- and alloantibodies that can develop against both endogenous and exogenous FVIII, respectively. Assessment for inhibitors represents a key part of the management of both congenital hemophilia A (CHA), an inherited deficiency, and acquired hemophilia A (AHA), an autoimmune condition.

Therapeutic Potential of Ketogenic Interventions for Autosomal-Dominant Polycystic Kidney Disease: A Systematic Review.

Background: Recent findings have highlighted that abnormal energy metabolism is a key feature of autosomal-dominant polycystic kidney disease (ADPKD). Emerging evidence suggests that nutritional ketosis could offer therapeutic benefits, including potentially slowing or even reversing disease progression. This systematic review aims to synthesise the literature on ketogenic interventions to evaluate the impact in ADPKD.

Portrait of a Cerebral Killer.

: Primary amebic meningoencephalitis (PAM) caused by is a rare and devastating infection of the central nervous system, often diagnosed late, due to its rapid progression and nonspecific symptoms. We report one of the youngest documented pediatric Vietnamese cases of PAM in a 10-month-old girl from the Mekong Delta, Vietnam. The diagnosis was confirmed through multiplex real-time PCR (MPL-rPCR), microscopy, and sequencing.

Outcomes With Radiation Therapy as Primary Treatment for Unresectable Cutaneous Head and Neck Squamous Cell Carcinoma.

Aims: Unresectable cutaneous squamous cell cancer of the head and neck (HNcSCC) poses treatment challenges in elderly and comorbid patients. Radiation therapy (RT) is often employed for locoregional control. This study aimed to determine progression-free survival (PFS) and overall survival (OS) outcomes achieved with upfront RT in unresectable HNcSCC.

Topical review: Ocular surface abnormalities in neurodegenerative disorders.

Significance: In an aging population, the number of people living with neurodegenerative disease is projected to increase. It is vital to develop reliable, noninvasive biomarkers to detect disease onset and monitor progression, and there is a growing body of research into the ocular surface as a potential source of such biomarkers.

Background: This article reviews the potential of in vivo corneal confocal microscopy and tear fluid analysis as tools for biomarker development.

Safety, Efficacy and Pharmacokinetics of daily optimised doses of Rifampicin for the Treatment of Tuberculosis: A Systematic Review and Bayesian Network Meta-Analysis.

Background: Higher than standard doses of rifampicin could improve the treatment outcome of drug-susceptible tuberculosis without compromising the safety of patients.

Methods: We performed a systematic review of prospective clinical studies including adults with pulmonary and extrapulmonary TB receiving rifampicin doses above 10mg/kg/day. We extracted the data on overall adverse events (AE), hepatic AE, sputum culture conversion (SCC) at week 8, recurrence, mortality, and pharmacokinetics.

Restoring Autophagy by Exercise Ameliorates Insulin Resistance Partly via Calcineurin-Driven TFEB Nuclear Translocation.

Exercise activates autophagy and lysosome system in skeletal muscle, which are known to play an important role in metabolic adaptation. However, the mechanism of exercise-activated autophagy and lysosome system in obese insulin resistance remains covert. In this study, we investigated the role of exercise-induced activation of autophagy and lysosome system in improving glucose metabolism of skeletal muscle.

Protracted Tuberculosis Outbreak in a Pasifika Diaspora in Western Sydney, Australia: The Importance of Community Engagement.

A prolonged tuberculosis outbreak, linked by whole-genome sequencing, occurred in a Pasifika extended family over 10 years (2013-2022) in Sydney, Australia. Despite Australia's low tuberculosis incidence, social and cultural complexities, and coronavirus disease 2019 (COVID-19) disruptions exacerbated transmission. Control required culturally sensitive, family-centered care and robust health system engagement.

Provision of continuous renal replacement therapy in children in intensive care in Australia and New Zealand.

Objectives: The objective of this study was to describe current use, clinical practice, and outcomes of continuous renal replacement therapy (CRRT) in children in the intensive care unit (ICU) in Australia and New Zealand.

Design: retrospective, binational registry-based cohort study and electronic survey of clinical practice.

Setting: ICUs that contribute to the Australian and New Zealand Paediatric Intensive Care Registry and a survey conducted in November 2021 including ICUs accredited for paediatric intensive care training that provide CRRT for children were part of this study.

Anaesthetic management of a large multi-nodular goitre with dynamic bilateral carotid artery compression.

Dynamic carotid compression arising from a change in patient position is a rare complication of goitre, with the potential for cerebral ischaemia and infarction. In this report, a 37-year-old woman presented with a multi-nodular goitre with clinical features concerning for transient cerebral ischaemia. The anaesthetic management and neurological monitoring used to mitigate the risk of cerebral ischaemia during thyroidectomy is described and the literature surrounding this rare complication is explored.

Predictors of Cryptococcus gattii clinical presentation and outcome: An international study.

Background: Infection by Cryptococcus gattii can lead to pulmonary or central nervous system (CNS) disease, or both. Whether site of infection and disease severity are associated with C. gattii species and lineages or with certain underlying medical conditions, or both is unclear.

Is minimally invasive glaucoma surgery killing trabeculectomies?

Purpose Of Review: The introduction of minimally invasive glaucoma surgery (MIGS) has changed the surgical landscape of glaucoma surgery. For more than four decades, the most commonly performed glaucoma surgery around the world has been the trabeculectomy. This article examines whether trabeculectomy is still the predominant procedure in glaucoma today, in the context of rapidly emerging MIGS devices and procedures.

Mechanisms and Therapeutic Potential of Multiple Forms of Cell Death in Myocardial Ischemia-Reperfusion Injury.

Programmed cell death, especially programmed necrosis such as necroptosis, ferroptosis, and pyroptosis, has attracted significant attention recently. Traditionally, necrosis was thought to occur accidentally without signaling pathways, but recent discoveries have revealed that molecular pathways regulate certain forms of necrosis, similar to apoptosis. Accumulating evidence indicates that programmed necrosis is involved in the development of various diseases, including myocardial ischemia-reperfusion injury (MIRI).

β-Cell Deletion of Hypoxia-Inducible Factor 1α (HIF-1α) Increases Pancreatic β-Cell Susceptibility to Streptozotocin.

Type 1 diabetes (T1D) is caused by the immune-mediated loss of pancreatic β-cells. Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor which is crucial for cellular responses to low oxygen. Here, we investigate the role of β-cell HIF-1α in β-cell death and diabetes after exposure to multiple low-dose streptozotocin (MLDS).

The mPower (Mother's Power) Initiative: Improving Health Behavior Through Peer Support and Health Literacy for Mothers of Children with Cerebral Palsy in Rural Bangladesh.

Background/objectives: Cerebral palsy (CP) affects a substantial number of children, particularly in low- and middle-income countries such as Bangladesh. Maternal health literacy is critical to the health and well-being of children with CP, particularly in low-resource settings. In this study, we sought to assess how the mPower (mother's power) community-based intervention impacted mothers' CP-specific knowledge, as well as their utilization of rehabilitation services in rural Bangladesh.

Microdissection of Distinct Morphological Regions Within Uveal Melanomas Identifies Novel Drug Targets.

: Uveal melanomas (UMs) are rare but often deadly malignancies that urgently require viable treatment options. UMs often exhibit tumour heterogeneity, with macroscopic and microscopic differences in morphology between different regions of the same tumour. However, to date, the clinical significance of this and how it may help guide personalised therapy have not been realised.

Surgeons' views on hypospadias care journey: A qualitative study.

Background: Three major parties are involved in the hypospadias treatment journey - the patient, their parents/carers, and the surgeon. There is a strong trend towards involving all three, where possible, in deriving evidence around the care pathways. Currently, there are little data available on surgeons' perspectives of distal hypospadias care.